Diagnostic and predictive testing for juvenile polyposis syndrome (JPS) or JPS/hereditary hemorrhagic telangiectasia.
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 2 mL)
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
Background Information for Juvenile Polyposis (SMAD4) Sequencing and Deletion/Duplication:
Characteristics of Juvenile Polyposis Syndrome (JPS): Gastrointestinal (GI) bleeding, multiple hamartomatous polyps in the GI tract, increased risk for GI carcinoma.
Characteristics of JP/Hereditary Hemorrhagic Telangiectasia (HHT): Recurrent nosebleeds, telangiectases (mouth, face, hands, GI tract), arteriovenous malformations (lung, brain, liver, spine) and hamartomatous polyps in the GI tract.
Incidence: 1 in 16,000 to 1 in 100,000 for JPS; unknown for JP/HHT.
Inheritance: Autosomal dominant; de novo mutations occur in 25 percent of JPS.
Penetrance: Suspected to be greater than 90 percent for JPS.
Cause for JPS: Mutations in SMAD4, BMPR1A and other unknown genes.
Cause for JP/HHT: Mutations in SMAD4.
Clinical Sensitivity: Approximately 25 percent for JPS; unknown for JP/HHT.
Methodology: Bidirectional sequencing of the entire SMAD4 coding region and intron-exon boundaries. Multiplex ligation-dependent probe amplification (MLPA) to detect large SMAD4 coding region deletions/duplications.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Breakpoints for large deletions/duplications will not be determined. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.
Laboratory Developed Test (LDT)
|Component Test Code*||Component Chart Name||LOINC|
|2001973||JPS (SMAD4) Seq and Del/Dup Interp|
|2001975||SMAD4 FGA Specimen|
- SMAD4 sqeuending and deletion/duplication